诱导型神经干细胞移植抑制颅脑创伤后补体活化的影响

目的研究诱导型神经干细胞（iNSCs）移植对颅脑创伤（TBI）后补体活化的影响。 方法采用自由落体脑打击装置制备雄性成年C57BL/6小鼠TBI模型，将30只神经功能缺损评分（NSS）为4~8分的小鼠纳入TBI组，按照随机数字表法选取10只用于制备TBI小鼠血清和热灭活TBI小鼠血清，余下20只按照按照随机数字表法分为：iNSCs移植组（10只）和磷酸缓冲盐溶液（PBS）处理组（10只）。同时设置假手术（sham）组（10只）。于TBI后12 h，分别将含5×10⁶个iNSCs单细胞悬液或等体积PBS经尾静脉注射到TBI小鼠体内，于移植后7 d处死动物，取脑组织行双重免疫荧光染色，观察iNSCs移植对TBI小鼠脑内C3d和NeuN抗体双阳性、C5b-9和NeuN抗体双阳性、C3d和Map2抗体双阳性以及C5b-9和Map2抗体双阳性的神经细胞的影响。于TBI后12 h，制备TBI小鼠血清和热灭活TBI小鼠血清，分别处理iNSCs后用流式细胞仪检测iNSCs表达补体调节分子Crry、Cd46、Cd59a和Cd55水平。 结果双重免疫荧光染色示：相比sham组，TBI小鼠脑组织中明显可见C3d和C5b-9沉积于NeuN和Map2抗体阳性的神经细胞；相比PBS处理组，iNSCs移植组TBI小鼠脑内C3d和NeuN抗体双阳性、C5b-9和NeuN抗体双阳性、C3d和Map2抗体双阳性以及C5b-9和Map2抗体双阳性的神经细胞数量均明显下降，2组差异具有统计学意义（P<0.05）。流式细胞仪检测示：相比热灭活TBI小鼠血清组，TBI小鼠血清组中iNSCs补体调节分子Crry表达水平明显上调，差异具有统计学意义（P<0.05）。 结论经静脉移植iNSCs可抑制TBI后补体活化，减轻神经损伤。     

A machine learning-based prediction model for in-hospital mortality among critically ill patients with hip fracture: An internal and external validated study

IntroductionFew studies have investigated the in-hospital mortality among critically ill patients with hip fracture. This study aimed to develop and validate a model to estimate the risk of in-hospital mortality among critically ill patients with hip fracture.MethodsFor this study, data from the Medical Information Mart for Intensive Care III (MIMIC-III) Database and electronic Intensive Care Unit (eICU) Collaborative Research Database were evaluated. Enrolled patients (n=391) in the MIMIC-III database were divided into a training (2/3, n=260) and a validation (1/3, n=131) group at random. Using machine learning algorithms such as random forest, gradient boosting machine, decision tree, and eXGBoosting machine approach, the training group was utilized to train and optimize models. The validation group was used to internally validate models and the optimal model could be obtained in terms of discrimination (area under the receiver operating characteristic curve, AUROC) and calibration (calibration curve). External validation was done in the eICU Collaborative Research Database (n=165). To encourage practical use of the model, a web-based calculator was developed according to the eXGBoosting machine approach.ResultsThe in-hospital death rate was 13.81% (54/391) in the MIMIC-III database and 10.91% (18/165) in the eICU Collaborative Research Database. Age, gender, anemia, mechanical ventilation, cardiac arrest, and chronic airway obstruction were the six model parameters which were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) method combined with 10-fold cross-validation. The model established using the eXGBoosting machine approach showed the highest area under curve (AUC) value (0.797, 95% CI: 0.696-0.898) and the best calibrating ability, with a calibration slope of 0.999 and intercept of -0.019. External validation also revealed favorable discrimination (AUC: 0.715, 95% CI: 0.566-0.864; accuracy: 0.788) and calibration (calibration slope: 0.805) in the eICU Collaborative Research Database. The web-based calculator could be available at https://doctorwangsj-webcalculator-main-yw69yd.streamlitapp.com/.ConclusionThe model has the potential to be a pragmatic risk prediction tool that is able to identify hip fracture patients who are at a high risk of in-hospital mortality in ICU settings, guide patient risk counseling, and simplify prognosis bench-marking by controlling for baseline risk.     

Clinical and Genetic Features of Brainstem Glioma in Adults: A Report of 50 Cases in a Single Center

Background and PurposeBrainstem gliomas (BSGs) in adults are rare brain tumors with dismal outcomes. The aim of this study was to determine the clinical and genetic features in a series of BSGs and their association with the prognosis.MethodsFifty patients who underwent a stereotactic biopsy between January 2016 and April 2018 at a single institution were collected. Data on clinicopathological characteristics were analyzed and factors associated with patient survival were identified using a Cox regression model.ResultsThe median age at diagnosis was 55.5 years, and 62% of the patients were male. Glioblastoma (44%) accounted for the largest proportion of BSGs, and oligodendroglioma (2 of 50) was rarely encountered. The IDH mutation (6 of 44) occurred infrequently in astrocytomas, and IDH-mutant tumors harbored both ATRX loss and MGMT promoter methylation at a relatively low level. Wild-type IDH astrocytomas were identified as having high rates of 1p/19q codeletion (5 of 38) and loss of heterozygosity 1p (8 of 38) or 19q (8 of 38) only. In diffuse midline glioma H3K27M mutant, MGMT promoter methylation occurred in three of four cases. Patients were offered radiotherapy and/or concurrent/adjuvant temozolomide chemotherapy, and their median survival time was 13 months. Multivariate analysis revealed that a low tumor grade, absence of tumor enhancement, duration of symptoms ≥3 months, Karnofsky performance status ≥70, and ATRX loss conferred a survival advantage.ConclusionsAdult BSGs showed different molecular genetic characteristics, but also resembled supratentorial gliomas in their clinical features associated with oncological outcomes.     

Psychiatry to dermatology; panic disorder

ObjectiveAnxiety is commonly observed together with skin diseases and can aggravate them, while skin diseases can increase anxiety. The relationship of skin diseases observed in panic disorder with quantitative electroencephalography (QEEG) findings has not been investigated yet. The aim of this study is to compare the absolute alpha and delta power of panic disorder patients with and without skin disease.Methods246 panic disorder patients, 19 of whom had skin disease and 227 of whom did not have skin disease, were included in the study. Panic disorder severity scale (PDSS) scores of patients were recorded, and QEEG recording was performed. Absolute alpha and delta power and PDSS scores were compared between the two groups.ResultsIt was found that the absolute delta power in the left hemisphere was lower and PDSS scores were higher in the patients with skin diseases compared to the control group. In the patients with skin disease, decreased delta power in the left hemisphere may cause impairment in the processing of positive emotions and may cause trait anxiety.ConclusionTrait anxiety may increase susceptibility to skin diseases by disrupting cutaneous homeostasis resulting from the prolonged sympathetic nervous system activation.     

睡眠状况对老年人群心血管疾病发病的影响

 目的 探讨睡眠状况对老年人群心血管疾病发病的影响。方法 选择2020-05至2021-02解放军总医院第二医学中心就诊的408例老年患者作为调查对象,采用调查问卷搜集患者人口学特征、躯体健康指标、抑郁状况、生化指标等资料,采用匹茨堡睡眠质量指数量表(Pittsburgh sleep quality index,PSQI)评估患者睡眠状况,采用logistic多因素回归模型分析睡眠状况对老年人群发生心血管疾病的影响。结果 408例老年患者,共收回有效问卷401例,回收率为98.28%。88例患有心血管疾病,发病率为21.95%。145例睡眠不足(36.16%),118例睡眠适度(29.43%),138例睡眠过度(34.41%)。有心血管疾病的老年患者睡眠不足39例(44.32%)和睡眠过度37例(42.05%)的占比明显高于无心血管疾病的老年患者睡眠不足的106例(33.87%)和睡眠过度的101例(33.26%),且其睡眠质量明显低于无心血管疾病的老年患者,差异均有统计学意义(P<0.05)。Logistic回归分析模型显示,睡眠不足(OR=2.575,95%CI:1.709~3.866)、睡眠过度(OR=1.377,95%CI:1.009~2.014)及睡眠质量很差(OR=4.371,95%CI:2.044~9.336)均为老年心血管疾病的独立风险因素(P均<0.05)。结论 老年人群睡眠状况影响心血管疾病的发生,重视老年人群睡眠状况对预防心血管疾病具有重要意义。     

诱导型神经干细胞移植对颅脑创伤后神经营养因子分泌的影响

目的研究诱导型神经干细胞（iNSCs）移植对颅脑创伤（TBI）后神经营养因子分泌的影响。 方法采用自由落体脑打击装置制备雄性成年C57BL/6小鼠TBI模型，将神经功能缺损评分（NSS）4~8分者纳入TBI组，按照随机数字表法分为iNSCs移植组（12只）和磷酸盐缓冲液（PBS）处理组（9只）。同时设置假手术（sham）组（9只）。于TBI后12 h，用脑立体定向仪将含1×10⁶个iNSCs单细胞悬液或等体积PBS分别移植到TBI小鼠脑内，于移植后7 d处死动物。分别取脑组织mRNA（3只/组）行逆转录定量实时聚合酶链反应（RT-qPCR）和蛋白（6只/组）行酶联免疫吸附测定（ELISA），检测脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）表达量；取iNSCs移植组（3只）动物脑组织行免疫荧光染色，观察iNSCs移植物分泌BDNF和GDNF。 结果RT-qPCR示：相比sham组，TBI小鼠脑组织中Bdnf和Gdnf基因转录水平明显降低；相比PBS处理组，iNSCs移植组TBI小鼠脑组织中Bdnf和Gdnf基因转录水平明显升高，差异具有统计学意义（P<0.05）。ELISA示：相比sham组，TBI小鼠脑组织中BDNF和GDNF蛋白表达水平明显降低；相比PBS处理组，iNSCs移植组TBI小鼠脑组织中BDNF和GDNF蛋白表达水平明显升高，差异具有统计学意义（P<0.05）。免疫荧光染色示iNSCs移植组TBI小鼠脑内可见绿色荧光蛋白标记的iNSCs移植物迁移到达脑损伤区并表达BDNF和GDNF。 结论经脑立体定向移植iNSCs可在TBI后脑组织中合成分泌神经营养因子BDNF和GDNF，发挥神经营养作用。     

Automated Analysis of Doppler Echocardiographic Videos as a Screening Tool for Valvular Heart Diseases

ObjectivesThis study sought to develop a deep learning (DL) framework to automatically analyze echocardiographic videos for the presence of valvular heart diseases (VHDs).BackgroundAlthough advances in DL have been applied to the interpretation of echocardiograms, such techniques have not been reported for interpretation of color Doppler videos for diagnosing VHDs.MethodsThe authors developed a 3-stage DL framework for automatic screening of echocardiographic videos for mitral stenosis (MS), mitral regurgitation (MR), aortic stenosis (AS), and aortic regurgitation (AR) that classifies echocardiographic views, detects the presence of VHDs, and, when present, quantifies key metrics related to VHD severities. The algorithm was trained (n = 1,335), validated (n = 311), and tested (n = 434) using retrospectively selected studies from 5 hospitals. A prospectively collected set of 1,374 consecutive echocardiograms served as a real-world test data set.ResultsDisease classification accuracy was high, with areas under the curve of 0.99 (95% CI: 0.97-0.99) for MS; 0.88 (95% CI: 0.86-0.90) for MR; 0.97 (95% CI: 0.95-0.99) for AS; and 0.90 (95% CI: 0.88-0.92) for AR in the prospective test data set. The limits of agreement (LOA) between the DL algorithm and physician estimates of metrics of valve lesion severities compared to the LOAs between 2 experienced physicians spanned from ?0.60 to 0.77 cm² vs ?0.48 to 0.44 cm² for MV area; from ?0.27 to 0.25 vs ?0.23 to 0.08 for MR jet area/left atrial area; from ?0.86 to 0.52 m/s vs ?0.48 to 0.54 m/s for peak aortic valve blood flow velocity (V_max); from ?10.6 to 9.5 mm Hg vs ?10.2 to 4.9 mm Hg for average peak aortic valve gradient; and from ?0.39 to 0.32 vs ?0.31 to 0.32 for AR jet width/left ventricular outflow tract diameter.ConclusionsThe proposed deep learning algorithm has the potential to automate and increase efficiency of the clinical workflow for screening echocardiographic images for the presence of VHDs and for quantifying metrics of disease severity.     

S100A9 as a novel diagnostic and prognostic biomarker in human gastric cancer

Abstract

Objective: The morbidity and mortality of gastric cancer (GC) is high, but there are lack of the biomarkers for early diagnosis and progression of GC. We aimed to identify a novel biomarker for the growth and progression of GC.

Methods: The Cancer Genome Atlas (TCGA) database including 352 eligible patients was used to screen candidate genes related to the prognosis of GC. A proteomics analysis of Chinese Human Proteome Sketches (CHPS) including 84 eligible sample tissues was conducted to further identify candidate biomarkers. A series of in vitro assays were performed to investigate the functions of candidate proteins in GC. Next, to verify whether the candidate oncogene was associated with gastric carcinogenesis, we screened its expression levels using samples from 200 patients with chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia, or GC and healthy controls.

Results: According to the analyses of the TCGA database and CHPS, we found that S100A9 may be associated with the prognosis of GC. The results of proliferation, wound-healing and invasion assays, immunohistochemistry (IHC) and western blot showed that high levels of S100A9 in tissues were significantly associated with GC aggressiveness and a poor prognosis (p?<?.05). Furthermore, we found that the expression of S100A9 increased gradually during the process of gastric carcinogenesis (p?<?.05). The diagnostic sensitivity and specificity of S100A9 as a biomarker for early GC were 61.4% and 81.3%, respectively.

Conclusions: This study reveals that S100A9 may be a novel biomarker for the early diagnosis and prognosis of GC patients.     

Current Endovascular Approach in Adult Patients with Pulmonary Vein Stenosis: A State-of-the-Art Approach

Regarding to more invasive treatment of atrial arrhythmia (atrial fibrillation ablation) and pulmonary vein isolation (PVI), the rate of acquired pulmonary vein stenosis (PVS) is increasing and at present, PV ablation for AF has become the principal cause of PVS in adult patients. On the other way, by improvement in procedural techniques, equipment, and the experience of the operators, the incidence of PVS has been decreased. There is some controversy about the manner of follow-up of these patients and in most centers, just symptomatic patients are considered for imaging and treatment. Almost always, those with PV stenosis more than 70% or multiple PV involvement become symptomatic and if give them up without treatment, pulmonary symptoms and finally irreversible pulmonary hypertension will occurred. So, intensive pursue after the procedure is highly recommended. Whereas in pediatric patients with congenital or acquired PVS, the best treatment approach is surgery, in adult patients, the preferred type of treatment is the transcatheter intervention with high acute success rate. In this present review, we have scrutinized about the diagnostic modalities, the indications for intervention, the diverse treatment strategies, and principally clarify an accurate stepwise approach during transcatheter procedure.